Term
| What is the goal of primary hemostasis? |
|
Definition
|
|
Term
| What is von Willebrand Factor? |
|
Definition
meidates platelet adhesion to exposed extracell matric when the endothelial lining of blood vessel is damaged.
- in plasma and extracell matrix
- binds to receptor on the platelet memb and to collagen fibers in the tissue
- adhered platelets become activated by agents that increase the calcium concentration of platelets |
|
|
Term
| What's the end product of secondary hemostasis? |
|
Definition
| cascade of clotting factors -> fibrin crosslinked clot |
|
|
Term
| What initiates secondary hemostasis? |
|
Definition
| activated platelets and factors released from damaged tissue |
|
|
Term
| What are the four major players of clot formation? |
|
Definition
- Endothelial cells (when intact...inhibit blood clotting, form prostacyclin which inhibits platelet adhesion/aggregation)
- Subendothelial tissue (when exposed bc of damage, the platelets and CF bind to this tissue **extrinsic)
- Platelets (release prot and vasoactive amines after binding, CF become active on the surface of activated platelets)
- Clotting factors CF (Plasma prot that make a proteolytic cascade -> fibrinogen -> fibrin |
|
|
Term
| Where does fibirinogen bind during hemostasis? |
|
Definition
| Activated receptor on platelet membrane |
|
|
Term
| Is fibrin normally found in plasma? |
|
Definition
| No. it's precursor, fibrinogen, is |
|
|
Term
| what converts fibrinogen into fibrin? |
|
Definition
|
|
Term
| How is fibrinogen -> fibrin? |
|
Definition
Thrombin cleave 2 peptide bonds between Aalpha and Bbetachains -> Fibronopeptide A, B, +fibrin monomer
- once the monomers are formed, aggregate -> fibrous structure |
|
|
Term
| What crosslinks the fibrin? |
|
Definition
| F XIIIa (transgluaminase) |
|
|
Term
| What catalyzes Prothrombin -> THrombin + inactive fragment reaction? |
|
Definition
|
|
Term
| How is Vit K involved in clotting? |
|
Definition
| It's required for the synthesis of gama-carbocy-glutamate in the inactive particle cleaved from Prothrombin -> thrombin |
|
|
Term
| Which protease(s) are involved in the extrinsic pathway? |
|
Definition
F VIIa
- active only in the presence of tissue factor, a membrane glycoprotein exposed after injury of the blood VV |
|
|
Term
| Which pathway requires a charged surface for activation? |
|
Definition
|
|
Term
| Where do the intrinsic and extrinsic pathways converge? |
|
Definition
|
|
Term
| Intrinsic pathway initiation examples |
|
Definition
-microdamage
- epithelium is still mostly intact
- bacteria
- plaque -> turbulence |
|
|
Term
| Contact phase activation of the intrinsic pathway |
|
Definition
- need 2 proteases (Kallikrein, Factor XIIa)
- XII -> XI -> IX -> VIII ->*X->V |
|
|
Term
| Which steps require Ca? Phospholipids? |
|
Definition
Ca: all g-carboxyglutamate containing factors (prothrombin, Vii, IX, X)
PL: VIII, V |
|
|
Term
| Which steps require Tissue Factor? |
|
Definition
| both steps in the extrinsic pathway |
|
|
Term
| Which protease inhibitor is activated by heparin? |
|
Definition
| Antithrombin III (which does both intrinsic and extrinsic) |
|
|
Term
| What protein degrades fibrin clot? |
|
Definition
Plasmin
- exists in blood as precursor, Plasminogen |
|
|
Term
| What can activate the plasminogen/fibrin clot? |
|
Definition
- tissue type plasminogen activator (tPA)
- urokinase
- streptokinase
- streptokinase (activates allosterically w.o proteolytic cleavage) |
|
|
Term
|
Definition
|
|
Term
| What does prolonged bleeding time indicate? |
|
Definition
|
|
Term
| Activated partial thromboplastin time (uses) |
|
Definition
Tests intrinsic and common
**Heparin efficacy |
|
|
Term
|
Definition
extrinsic + commin
**Test for Coumadin efficacy |
|
|
Term
| What should you look at next if you have abnormal Hb and white blood count? |
|
Definition
| Look at the factory! Bone marrow examination |
|
|
Term
| What do clumped platelets in a peripheral blood smear indicate? |
|
Definition
| error! redraw in sodium citrate or heparin |
|
|
Term
| Hyperfunctional platelets |
|
Definition
| The platelets get bigger to do more as compared to cirrhosis of the liver. That's why you need such a low count before you see bleeding |
|
|
Term
|
Definition
| Immune/Idiopathic Thrombocytopenic Purpura |
|
|
Term
|
Definition
- Ab mediated platelet destruction in liver and spleen
- compensate w. increase in megakaryocyte number, size, and ploidy -> decrease platelet shedding |
|
|
Term
| What are the four important coagulation tests? |
|
Definition
Platelet count
aPTT- activated Prot? #48
PT- Prothrombin Time
Bleeding Time (not really used anymore) |
|
|
Term
| What can u miss w. the Big 4 coag tests? |
|
Definition
|
|
Term
|
Definition
- reach "safe" platelet count (>30,000)... Don't need "normal" bc they have super platelets
- if it's <30,000 or bleeding, Predinosone 1mg/kg 1/day po
- if that doesn't work, splenectomy (but only works on 60%) ***not really done anymore
- If that doesn't work = Chronic ITP needs Rituximab
- last resort - TPO mimetic agents |
|
|
Term
| What drugs do you use for ITP? |
|
Definition
1. Corticosteroids (prednisome, dexamethasone)
- Anti-inflammatory and immunosupressive.. decrease clearance of Ab-coated platelets by Macro's ... but can cause adrenal suppression, GI, etc
2. Intravenous immunoglobulin (IVIG)
3. Anti-D immunoglobulin (Win-Rho)
4. Rituximab (Rituxan)
5. THrombopoietin (TPO) Receptor Agonist |
|
|
Term
|
Definition
|
|
Term
|
Definition
- A recombinant monoclonal Ab
- targets CD20 Ag on B cells and decreases their ability to produce platelet-binding auto-Ab
- used for B cell non-Hodgkin's lymphomas and ITP |
|
|
Term
| What are the 2 TPO REceptor Agonists? |
|
Definition
|
|
Term
|
Definition
-Nplate
-fusion protein w 2 TPO (THrombopoietin) receptor-binding domains
-SC weekly |
|
|
Term
|
Definition
-Promacta
-orally
-nonpeptide
?? #58 |
|
|
Term
|
Definition
| Collection of blood in a joint? |
|
|
Term
| Prolonged PT and Normal aPTT |
|
Definition
Factor VII def (inherited or acquired)
Vit K def
liver disease
Coumadin administration
INhibitor of Factor VII |
|
|
Term
| Normal PT and prolonged aPTT |
|
Definition
Def of F VIII, IX, XI (inherited or acquired)
Def of F XII, prekallikrein,
von Willebrand disease |
|
|
Term
| Prolonged PT and prolonged aPTT |
|
Definition
Def of prothrombin, fibrinogen, or factors V or X
combined factor deficiencies
liver disease
DIC
Supratherapeutic doses of Heparin/coumadin
Inhibitor of prothrombin, fibrinogen, or factors V or X
Primary amyloidosis- associated factor X def |
|
|
Term
|
Definition
- Mucocutaneous bleeding
- epistaxis
-GI/GU sites
-bleeding after minor cuts
- Petechiae |
|
|
Term
|
Definition
Factor VIII def/F IX def *christmas disease
- X-linked recessive diseases
- uncommon in females
- usually diagnosed before 2yo
- sites of bleeding: Intracranial, joints, MM, H*N, GI, GU
- late complications: joint destruction bc of recurrent bleeds (need joint replacements ~30yo, transmission of blood-borne infections, development of inhibit Ab's |
|
|
Term
| How do you manage Hemophilia? |
|
Definition
*Factor Replacement Therapy
- A -> VIII
- B -> IX
...minor bleeding only needs 40% of factor
* Primary Prophylaxis - done early in life to prevent later complications
* Desmopressin: prevent bleeding and treat acute bleeding episodes in Pt w. mild Hemophilia A ... releases Factor VIII fr endothelial cells (ex. before dental work)
* Epsolon Aminocaproic Acid (EACA) ... increase clot stability by inhibiting fibrinolysis, adjunctive therapy for oral bleeding, epistaxis and menorrhagia ***Used w. factor replacements |
|
|
Term
| Where are most coagulation proteins made? |
|
Definition
|
|
Term
| What Hx is associated w. Liver Cirrhosis? |
|
Definition
ETOH abuse
VIral Hepatitis |
|
|
Term
| What labs would you expect w. Liver Cirrhosis? |
|
Definition
- ascites
- normal liver function tests (AST/ALT)
- shrunken, nodular liver (ultrasound) |
|
|
Term
| How would you confirm liver cirrhosis? (gold standard) |
|
Definition
| Liver Biopsy (80-100% sensitivity) |
|
|
Term
| DIC (Disseminated Intravascular Coagulation) labs |
|
Definition
- low platelets
- low serum fibrinogen *** indicates it's not just sepsis anymore
- elevated fibrin degradeation products and D-dimer
- Thrombocytopenia
- elevated PT and PTT |
|
|
Term
|
Definition
Septicemia
crush injury
etc |
|
|
Term
|
Definition
| Bleeding, jaundice, acute renal failure, coma, and pulmonary hemorrhage |
|
|
Term
|
Definition
- treat underlying cause
- platelet and Fresh Frozen plasma (prevent bleeding)... to keep fibrinogen level >100
- Heparin (sometimes/controversial) |
|
|
Term
| Some common Antigoagulants |
|
Definition
-Heparin: potentiates the action of Antithrombin and inactivates thrombin **check PTT
-Coumadin (warfarin): inhibits Vit K and decreases prod of F II, VII, IX, X, Proteins C and S **Check PT
-Argatroban: Direct Thrombin inhibitor |
|
|
Term
| International Standardized Ratio (INR) |
|
Definition
... should be 2-3
- standardize the PT across labs |
|
|
Term
| WHere do we get Vit K from? |
|
Definition
green veggies (spinach and broccoli)
intestinal bacteria |
|
|
Term
| What factors are vit K for? |
|
Definition
|
|
Term
|
Definition
- Antibiotics (reduce intestinal bacteria)
- prolonged starvation
- Total Parenteral nutrition (TPN)
- Coumadin-like anticoagulants |
|
|
Term
|
Definition
-easy bruising
-mucosal bleeding
-melena
-hematuria
-??? |
|
|
Term
|
Definition
| 1-25 mg of Vitamin K via PO, IM, SC, or IV routes |
|
|
Term
| What are the components of Virchow's Triad? |
|
Definition
1. Alterations in blood flow (ie. stasis)
2. Vascular endothelial injury (surgery)
3. Alterations in the constituents of the blood (inherited/acquired hypercoagulable state) |
|
|
Term
| What are some inherited thrombophilias? |
|
Definition
-Factor V Leiden
-Prothrombin gene mutation
-Protein S def (kinda rare)
-Protein C def (kinda rare) |
|
|
Term
| Acquired risk factors for venous thrombosis |
|
Definition
-Cancer
-Surgery
-Trauma
-pregnancy
-Oral contraceptives |
|
|
Term
|
Definition
Factor V Leiden is inactivated more slowly by activated Prot C causing it to stay longer in the ciculation which increases coagulation
*** causation isn't completely clear. Some ppl with it, never clot
*** Heterozygosity is 5% of caucasians... common |
|
|
Term
| Factor V Leiden Mutation Management |
|
Definition
1. oral anticoagulation (Warfarin (3-6mo))
2. Indefinite anticoagulation if:
- 2 or more spontaneous thromboses
- a spontaneous life-threatening thrombosis
- spontaneous thrombosis at an unusual site (mesenteric, cerebral vein)
- spontaneous thrombosis in the presence of more than 1 genetic defect (combined heterozygosity for prot S def, prot C, def, anthithrombin deg |
|
|
Term
|
Definition
-Indirect thrombin inhibitor
-Large charged molecule -> IM/SC |
|
|
Term
|
Definition
- Unfractionated heparin - accelerates interaction f antithrombin w. both thrombin and factor Xa
- Enoxaparin (lovenox) - low MW heparins SC 2x/day (doesn't need lab monitering)
- Fondaparinux |
|
|
Term
|
Definition
- Hemorrhage
- Heparin-induced thrombocytopenia (HIT) (Ab to H+platelet factor R) Monitor platelet count
-???
*** moniter w. TPP |
|
|
Term
| Direct Thrombin inhibitors |
|
Definition
1. Lepirudin (derivative of hirudin from leech)
2. Bivalirudin
3. Argatroban
4. Dabigatran
3.
4. ??? |
|
|
Term
| Direct Thrombin inhibitors (MOA) |
|
Definition
| prevent thrombosis by inhibiting thrombin and ***Prolong aPPT |
|
|
Term
| Direct Thrombin inhibitors Side Effects |
|
Definition
Hemorrhage (dose-related)
*** Does not cause thrombocytopenia |
|
|
Term
| Oral anticoagulants example and MOA |
|
Definition
Warfarin - inhibits Fit-K epoxide reductase
-> inhibits synth of vit K dependent clotting factors II, VII, IX and X
*competitive, surmountalbe
*site of Genetic resistence
- Rx interaction |
|
|
Term
| What does grapefruit juice do to Warfarin? |
|
Definition
- decrease the catabolism by enzyme inhibition
- increase activity |
|
|
Term
| What does antibacterial drugs do to Warfarin? |
|
Definition
|
|
Term
| Antiplatelet agents (Aspirin) MOA |
|
Definition
- block Cyclo-oxygenase -> less PGl2 and TXA2
**Low doses only reduce TXA2!! so the protective effects of PGI2 are still available |
|
|
Term
| ADP inhibitors: Thienopyridines examples |
|
Definition
|
|
Term
| Thrombolytic (fibrinolytic) Drugs |
|
Definition
- Tissue-type plasminogen activator, alteplase
- Streptokinase |
|
|
Term
| Thrombolytic (fibrinolytic) Drugs MOA |
|
Definition
| convert plasminogen to plasmin... degrades fibrin/fibrinogen/-> clot dissolution |
|
|
Term
| What are the typical labs for acute Myeloid Leukemia? |
|
Definition
-Hb low
- Platelet low
- WBC cell high |
|
|
Term
|
Definition
-Bone Marrow Biopsy
-Morphology of cells (core biopsy)
-Flow Cytometry
-Cytogenetics |
|
|
Term
| When/where do you see Auer rods? |
|
Definition
|
|
Term
|
Definition
-Blast Crisis of CML (Ph chromosome not in AML)
-Vit B12/Folate def (can be confusd w. Erythroleukemeia)
-Myelodysplastic syndrom (Refractory Anemia w. Excess Blasts) ... 5-19%... any more = AML
-Acute Lymphoblastic Leukemia (flow cytometry will differentiate) |
|
|
Term
| What do mutations of the stem cell or early blood cell precursors give rise to? |
|
Definition
|
|
Term
|
Definition
| completely arrest maturation early in blood cell development |
|
|
Term
| Myelodysplastic mutations |
|
Definition
| mutations that impair and slow blood cell maturation |
|
|
Term
| Myeloproliferative disorders |
|
Definition
| mutations that cause autonomous overproduction of mature blood cells and their immediate precursors |
|
|
Term
| Which leukemia is more common in children? |
|
Definition
| ALL (80% of all childhood leukemias) |
|
|
Term
| Which leukemia is more common in adults? |
|
Definition
| AML (80% of all adult leukemias) |
|
|
Term
| Genetic problems that can predispose to acute leukemia |
|
Definition
Down Syndrome
Bloom's Syndrome
Fanconi's Anemia (aplastic anemia)
Li-Fraumini Syndrome (p53 mutation) ... (familial clustering of certain cancers)
-Identical Twins |
|
|
Term
|
Definition
-Alkylating Agents (often precedes MDS) chemo drug
-Radiation
-benzene (industrial chem)
-Topoisomerase inhibitors (Doxorubicin= breast cancer drug ... cardiapathy?)
- HTLV-I virus (Human T Lymphotrophic Virus Type I |
|
|
Term
| AML Etiology: Pre-existing conditions |
|
Definition
Myeolodysplasia (MDS)
Myeloproliferative Disorders
Paroxysmal Nocturnal Hemoglobinuria
*** Leukemia from these conditions is usually resistant to treatment |
|
|
Term
|
Definition
-infiltrate/replace bone marrow/other organs
-normal production diminished -> severe anemia, hemorrage, infections (usually COD)
#25 |
|
|
Term
| Acute Leukemia major subtypes |
|
Definition
immature cells (blasts) comprise >20% of nucleated cells in BM specimen
*ALL (Acute Lymphoblastic Leukemia)
*AML (Acute Myelogenous Leukemia) |
|
|
Term
|
Definition
-Anemia -> fatigue, pallor, dyspnea
-Neutropenia -> fever from infections
-Thrombocytopenia -> easily bruised, petechia, bleeding
-NO hepatosplenomegal
-NO splenomegaly (only chronic) |
|
|
Term
|
Definition
M0 - no distinguishing morphology
M1 - few granules, rare auer rods, MP+
M2 - more granules, occ auer rods, MP+, t(8;21)
M3 - hypergranular, lotsa auer rods, MP+, t(15;17)
M4- Monocyte forms, NSE+, inv (16)
M5 - Monoblast, NSE+
M6 - Erythroblast, PAS+glycophorin A
M7 - Dysplastic Megakaryocytes, CD41, CD61, vWF |
|
|
Term
|
Definition
1. Classic: packed with Auer rods
2. Microgranular: smaller granules |
|
|
Term
| Why does AML M3 often cause DIC? |
|
Definition
cytoplasmic contents extrmemly disruptive of normal hemostasis ..
-DIC from Tissue Factor |
|
|
Term
|
Definition
ATRA (All Trans Retinoic A)
Vit A analogue |
|
|
Term
| AML chromosomal Translocation |
|
Definition
t(15;17) -> inactivates transcription factors
- creates PML-RARalpha ... disables Retinoic acid receptor function... blocks myeloid differentiation
Tx w. ATRA ... good results!! |
|
|
Term
| What's the treatment of AML M3? |
|
Definition
|
|
Term
| AML-M5 organ involvement pattern |
|
Definition
Mucous membranes: gume hypertrophy
Skin: leukemia cutis
CNS: cranial N palsies |
|
|
Term
|
Definition
-from erythroid(6) or megakaryocyte(7)
-poor prognosis
-Flow cytometry for surface phenotypes are the most helpful in diagnosing |
|
|
Term
| AML Bad prognostic factors |
|
Definition
-Age >60yo
-Antecedent hematologic disorder
-Wbc>20,000 at Dx
-CNS involvement at Dx |
|
|
Term
| Does acute leukemia always have lots of WBC count in peripheral blood? |
|
Definition
No... can be packed in bone marrow
*** usually seen in peripheral for chronic ML |
|
|
Term
| AML: Cytogenetic Prognostic Factors |
|
Definition
Worsens: tyrosine kinases FLT-3, C-KIT
Improves: NPM1 (Nucleophosmin Member1), CEBP-A (CCAAT/Enhancer Binding Protein Alpha) |
|
|
Term
| AML Tx: Anthracycline Antibiotics |
|
Definition
4 membered anthracene ring..
Multiple Mechanisms
-intercalates DNA
-Inhibit Topo II -> DNA damage
-***increases O2 Free Radicals -> Scission of DNA
- *Daunorubicin HCl
- *Doxorubicin HCl (usually used in combo w. cytarabine... broad spectrum... ***breast, endometrium, acute leukemia, hodgkin's ABVD) |
|
|
Term
|
Definition
-Bone toxicity
-Red urine
-***Cardiomyopathy (cumulative, dose related, irreversible-> Congestive Heart Failure, Arrhythmias) |
|
|
Term
|
Definition
Antimetabolites...
MOA: activated triphosphate form inhibits DNA pol and synthesis by competing with DNA bases
Se: Myelosupression, mucositis, flu-like Sx
-Cytarabine (arabinose)
-Gemcitabine HCl |
|
|
Term
| What is the DOC for pancreatic cancer? |
|
Definition
|
|
Term
|
Definition
-Stabilize the Pt first!! Bone marrow biopsy to determine the right kind of chemo to use
-Remission Induction
-Regiment: 7+3 (Daunorubicin for 3d and standard dose Cytarabine for 7d) ... must be monitored!
-Redo the BM biopsy
**Good result -> consolidation regiment
**Bad result -> 7+3 again.. if still bad -> hospice |
|
|
Term
| Why does the 7+3 regiment need to be monitored? |
|
Definition
*** BM is almost wiped clean!
watch out for cytopenias, infections, bleeding, tumor lysis syndrome, electrolyte imbalances |
|
|
Term
|
Definition
-gradually worsening fatigue
-abd pain
-pallor
-LUQ abd tenderness
- fever, night sweats, weight loss (due to spelnomegaly and hypermetabolic state)
-Splenomegaly |
|
|
Term
|
Definition
|
|
Term
|
Definition
| -tons of diff myelocytes at diff stages of development |
|
|
Term
|
Definition
| - Philadelphia Chromosome??? |
|
|
Term
|
Definition
1. Leukemoid reaction
- due to serial infections
- smear: Toxic Granulations and Dohle Body
- elevated leukocyte alkaline phosphatase score (decreased in CML)
-no Phill chromosome
2. Juvenile Myeolomonocytic leukema
- wrong age (infancy and childhood)
3. Chronic Myelomonocytic Leukemia
- Myelodysplastic disorder
- overproduction of maturing monocytic cells
-Dysplastic changes in myeloid lineage
-Ph chrom (-) |
|
|
Term
| Myeloproliferative Disorders |
|
Definition
1. Chronic Myelogenous Leukemia (mature granulocytes)
2. Polycythemia Rubra Vera (PV) lotsa RBC
3. Essential??? #62 |
|
|
Term
| Can CML turn into AML or ALL? |
|
Definition
|
|
Term
| What's the DOC for PV and ET? |
|
Definition
|
|
Term
| myelogenous disorders almost always have.... |
|
Definition
|
|
Term
| What are the three phases of CML? |
|
Definition
1Chronic (stable 3-5 yrs) **most often seen
2. Accelerated phase ~6 mo
3. Blast crisis phase (lymphoid or myeloid) *** Terminal event if not treated |
|
|
Term
|
Definition
-philadelphia chr (translocation between ch9 and 22)
- BCR-ABL |
|
|
Term
|
Definition
| 1. Tyrosine Kinase inhibitors |
|
|
Term
| Tyrosine Kinase inhibitors |
|
Definition
1. Imatinib mesylate
2. Dasatinib
- used to treat CML
-MOA: binds Bcr-ABL and inhibits the Tyrosine Kinase enzyme created my their junction and inhibits cell proliferation |
|
|
Term
| What's the first line Tx for CML Ph (+)? |
|
Definition
Imatinib
-80% effective
-Remission >1yr |
|
|
Term
| What do you use for Pt that are resistant to Imatninib?D |
|
Definition
|
|
Term
| Tyrosine Kinase inhibitor (Imatinib) SE |
|
Definition
-NVD, edema, mm cramps, pleural effusion
- dasatinib is more myelosuppressive |
|
|
Term
|
Definition
-Tyrosine Kinase Inhibitors (1st/2nd generation)
- allogenic bone marrow transplantation(not used as much now bc of efficacy of drugs |
|
|
Term
|
Definition
- burning pain in hands feet
- fatigue
-headaches
-skin itching after a warm bath (pruritis)
-Gout, peptic ulcer disease, hemorrhage, thrombosis (bc increased viscosity in blood)
-facial plethora
-splenomegaly
-> marrow fibrosis |
|
|
Term
|
Definition
-WBC high
-Hb high
*** all are elevated... factory problem
-Platelet high |
|
|
Term
| When do you see erythrocytosis? |
|
Definition
| PCV or essential thrombocytosis |
|
|
Term
| What do you suspect if just Hb is high? |
|
Definition
elevated EPO
-inappropriate (hepatocellular carcinoma, etc)
-appropriate (hypoxia due to sleep apnea, high altitude, etc) |
|
|
Term
|
Definition
| - Jak2-serum test (only present in PCV) |
|
|
Term
|
Definition
Major -
- arterial o2 sat >92% (rule out 2dary polycythemia)
-increased Red cell mass
-Splenomeagly
Minor
-platelet count > 400/L
-WBC
L.... #85 |
|
|
Term
|
Definition
|
|
Term
|
Definition
HYDROXYUREA
-MOA: decrease ribonucleotide reductase -> decrease deoxynucleoside triphosphate pools -> less DNA synth in S phase
-Clinical use: Myeloproliferative disease (PCV, Essential THrombocytosis. or Sickle Cell
-SE: myelosupression- dose limiting
... NVD, mucositis, headache, skin rash w. pruritus |
|
|
Term
|
Definition
-Phlebotomy ... keep Hb less than 15g/dl
-Hydroxyurea if platelet count is elevated
-Aspirin ... prevent thrombosis |
|
|
Term
|
Definition
Bone Marrow fibrosis associated w. increased cytokines fr. clonoal prolif of megakaryocytes, monocytes, and histiocytes.
-HUGE SPLEENS
-Smear: Teardrop erythrocytes + Leucoerythroblastic picture, early granuloctye and erythroid precursors
-BM: strongly positive for reticulin stain for fibrosis |
|
|
Term
|
Definition
-from extramedulary hematopoesis
-splenomegaly!
-anemia
-bleeding, thrombosis, hypermotabolic Sx (night sweats, weight loss)
-median survival is 5 yrs...
-no Tx |
|
|
Term
| Essential THrombocytosis labs |
|
Definition
|
|
Term
| Secondary thrombocytosis is due to |
|
Definition
|
|
Term
| Essential Thrombocytosis Sx |
|
Definition
| due to vasomotor distubances, thromboticevents, bleeding #94 |
|
|
Term
|
Definition
|
|
Term
|
Definition
-displastic RBC (increase central area of pallor)
-no blasts |
|
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Term
|
Definition
-WBC normal
-Hb low
-Macrocytic
-Platelets Low |
|
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Term
What are some causes of Macrocytosis?
**KNOW |
|
Definition
-B12/Folate
-Drugs (Hydroxyurea, Methotrexate)
-Shift to immature/stressed red cells (BM is in a hurry! reticulocytosis, pure red cell aplasia... parvo virus b-19)
-Primary BM disorders (Myeolodysplastic syndromes)
-Hyperthyroidism
-other (liver disease, myeloma, EtOH abuse) |
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Term
|
Definition
-reticulocyte count
-b12, folate, TSH
#103?? |
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Term
| Myelodysplastic Syndroms Epidemiology |
|
Definition
-disease of late adulthood
- incidence increases w. age >50
- can go to AML |
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Term
| Myelodysplastic syndrome (MDS) patho |
|
Definition
defective maturation in all three lineages
-anemia, neutropenia, thrombocytopenia, dysfunctional cells
*5q- chromosomal abnormalities possilbe |
|
|
Term
| Myelodysplastic Syndromes classification |
|
Definition
-Peculiar cellular morphology
*Refractory Anemia with Ringed Sideroblasts (FS in marrow w iron stain)
*CMMol, Chronic Myelomonocytic Leukemia (lotsa circulating monocytes
-Number of Marrow Blasts
#109???? |
|
|
Term
| 5q- syndrome of Myelodysplastic syndrom |
|
Definition
-older females
-macrocytosis
-normal/elevated platelets
-BM has abnormal megas (monolobulated/bilobulated micromegakayocytes)
-2/3 have RARS, 1/3 have RAEB
-**** unique response to Lenalidomide |
|
|
Term
| Myelodysplastic Syndrome Tx |
|
Definition
1. Hematopoietic Growth Factors:
*Epoetin Alfa
-MOA: replace EPO... normally produced by peritubular cells in prox tubule of kidney in response to hypoxia... a 34-39 kDA glycoprotein
*synthesized by
-clinical use:
* Anemia in chronic renal failure, cancer, AIDS, MDS
*before surgery
2. Myeloid Growth Factors
3. Decitabine |
|
|
Term
|
Definition
-Toxicity
hypertension (clotting, DVT)
Black Box Warning (CRF and Cacner pt increased risk ... above and tumor pregression, death
*** watch Hb... keep it below 12g/dL |
|
|
Term
|
Definition
| athletic performance enhancer |
|
|
Term
|
Definition
replacement therapy for neutropenia
*Filgrastim
*Sargramostim
- increase proliferation of neutrophils, mono, etc
- clinical use:
*chemo induced neutropenia
*myeloid recovery after BM transplant
*mobilization of peripheral blood stem cells
-SE: mild |
|
|
Term
|
Definition
-MOA: cytosine nucleoside analog... incorporated, prevent methylation -> antileukemic activity and increase differentiation
-Uses: MDS ...IV
-SE: myelosuppression, severe NV |
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|
Term
|
Definition
| -Growth Factors???? last slide |
|
|
Term
|
Definition
-longer
-initiated by the KKK (Kaolin, preKallikrein, HiMW Kininogen)
- measured by PTT
- occurs in vitro and as part of the amplification phase of coagulation - Big THrombin Amounts
- TENET (12,11,9,8,10) |
|
|
Term
| Extrinsic Pathway ... Key Points |
|
Definition
- Shorter pathway/activation time
- VIIa -> X
- measured by PT
- little thrombin amounts |
|
|
Term
| What is the fastest way to distinguish AML from ALL? |
|
Definition
|
|
Term
|
Definition
- looks like promyelocytes
- Acute Promyelocytic Leukemia (APL)
-Largest cells of any Acute Leukemia
-2 morphologic subtyptes
-rearrangements involving chromosome 17 |
|
|
Term
| What is the most lethal type of AML if untreated but has the best long term prognosis if initial treatment period is successful? |
|
Definition
|
|
Term
| How does AML M3 usually present? |
|
Definition
| Severe mucosal bleeding, life threatening CNS bleeds, extensive ecchymosis |
|
|
Term
|
Definition
| Erythroid antigens = glycophorin A |
|
|
Term
| AML M7 surface markers for flow cytology |
|
Definition
CD41 (gpIIb/IIIa)
CD61 (gpIIa)
vWF |
|
|
Term
|
Definition
MOA- free radicals cause cardiac damage... prevent with ***dexraxzoxane (chelates Fe to prevent ROS)
-* use in small doses, IV infusion, Liposomal DOXO |
|
|
Term
| Daunorubicin Clinical uses |
|
Definition
|
|
Term
| Doxorubicin: clinical uses |
|
Definition
-broad spectrum chemotherapy Rx
-breast, endometrium, ovary, thyroid, lung carcinomas
-Acute leukemia, Hodgkin's (ABVD), NHL (CHOP) |
|
|
Term
| Cytarabine: clinical uses |
|
Definition
| - induction of remission in AML, lung, ovary, pancreas cancer |
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